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ObjectiveTo investigate the effect of Tangbikang granules on oxidative stress of sciatic nerve in diabetic rats by regulating adenylate activated protein kinase/peroxisome proliferator-activated receptor γ coactivator-1α/mitochondrial Sirtuins 3 （AMPK/PGC-1α/SIRT3） signaling pathway. MethodThe spontaneous obesity type 2 diabetes model was established using ZDF rats. After modeling， they were randomly divided into high， medium， and low dose Tangbikang granule groups （2.5， 1.25， 0.625 g·kg-1·d-1） and lipoic acid group （0.026 8 g·kg-1·d-1）， and the normal group was set up. The rats were administered continuously for 12 weeks after modeling. The blood glucose of rats was detected before intervention and at 4， 8， 12 weeks after intervention. At the 12th week， motor nerve conduction velocity （MNCV）， sensory nerve conduction velocity （SNCV）， nerve blood flow velocity， mechanical pain threshold， and thermal pain threshold were detected. The sciatic nerve was taken for hematoxylin-eosin （HE） staining to observe the tissue morphology. The ultrastructure of the sciatic nerve was observed by transmission electron microscope. The expression levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in sciatic nerve were determined by enzyme-related immunosorbent assay （ELISA）. The mRNA expressions of AMPKα， AMPKβ， PGC-1α， and SIRT3 in sciatic nerve were determined by real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， fasting blood glucose in the model group was increased at each time point （P<0.01）. The mechanical pain threshold was decreased （P<0.05）， and the incubation time of the hot plate was extended （P<0.01）. MNCV， SNCV， and nerve blood flow velocity decreased （P<0.05）. The expression level of SOD was decreased （P<0.01）. The expression levels of MDA， IL-1β， and TNF-α were increased （P<0.01）. The mRNA expression levels of AMPKα， AMPKβ， PGC-1α， and SIRT3 were decreased （P<0.01）. The structure of sciatic nerve fibers in the model group was loose， and the arrangement was disordered. The demyelination change was obvious. Compared with the model group， the fasting blood glucose of rats in the high dose Tangbikang granule group was decreased after the intervention of eight weeks and 12 weeks （P<0.01）. The mechanical pain threshold increased （P<0.05）. The incubation time of the hot plate was shortened （P<0.01）. MNCV， SNCV， and Flux increased （P<0.05）. The expression level of SOD was increased （P<0.01）. The expression levels of MDA， IL-1β， and TNF-α were decreased （P<0.01）. The mRNA expression levels of AMPKα， AMPKβ， PGC-1α， and SIRT3 were increased （P<0.01）. The sciatic nerve fibers in the high-dose Tangbikang granule group were tighter and more neatly arranged， with only a few demyelinating changes. The high， medium， and low dose Tangbikang granule groups showed a significant dose-effect trend. ConclusionTangbikang granules may improve sciatic nerve function in diabetic rats by regulating AMPK/PGC-1α/SIRT3 signaling pathway partly to inhibit oxidative stress.
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Objective To investigate the relationship between mean platelet volume/lymphocyte ratio(MPVLR)and left atrial thrombosis in elderly patients with non-valvular atrial fibrillation(NVAF).Methods A total of 178 elderly patients with NVAF admitted to the hospital from January 2019 to December 2022 were enrolled in the study.The patients were divided into thrombosis group(28 cases)and non-throm-bosis group(150 cases)according to the left atrial thrombosis judged by using esophageal echocardiography(TEE).The white blood cell count(WBC),red blood cell count(RBC),lymphocyte count,lymphocyte pro-portion,platelet count(PLT)and mean platelet volume(MPV)were detected by automatic blood cell analy-zer,and MPVLR was calculated.The liver and kidney function indicators and blood lipid indicators were detec-ted by automatic biochemical analyzer.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of MPV,lymphocyte ratio and MPVLR for left atrial thrombosis in NVAF patients.Multiva-riate Logistic regression was used to analyze the influencing factors of left atrial thrombosis in elderly NVAF patients.Results MPV,lymphocyte proportion and MPVLR in the thrombosis group were higher than those in the non-thrombosis group,and the differences were statistically significant(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of MPV,lymphocyte ratio and MPVLR for predicting left atrial thrombosis in NVAF patients were 0.821(95％CI:0.764-0.882),0.771(95％CI:0.714-0.842)and 0.901(95％CI:0.861-0.949).respectively.The course of disease in the thrombosis group was longer than that in the non-thrombosis group,the proportion of patients with chronic heart failure,the proportion of patients with stroke,CH A2DS2-VASc score,LAEF,LAD,LVEDV,MPVLR,serum uric acid,MPV,lymphocyte proportion and MPVLR were higher than those in the non-thrombosis group,and LVEF was lower than that in the non-thrombosis group,the differences were statistically significant(P＜0.05).Multivariate Logistic regression a-nalysis showed that disease duration ≥1.93 years(OR=3.050,95％CI:1.928-4.824),chronic heart failure(OR=3.333,95％CI:1.808-6.144),MPVLR≥3.10(OR=3.873,95％CI:1.734-8.650)were independ-ent risk factors for left atrial thrombosis in elderly NVAF patients(P＜0.05).Conclusion The increase of MPVLR is associated with left atrial thrombosis in elderly patients with NVAF,and it can be used as a an in-dicator to predict left atrial thrombosis in patients with NVAF.
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BACKGROUND:Shujin Jiannao Prescription is an empirical formula for the treatment of cerebral palsy in Dongzhimen Hospital,Beijing University of Chinese Medicine,with clear clinical efficacy,but the specific mechanism needs to be elucidated. OBJECTIVE:To explore the possible mechanism of Shujin Jiannao Prescription in treating cerebral palsy. METHODS:Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into a normal group(n=12)and a model group(n=52).An animal model was established by the Rice-Vannucci method.After successful modeling,52 model rats were randomly divided into control model group(n=12),minocycline group,and the low-,medium-,and high-dose groups of the Shujin Jiannao Prescription(n=10 per group).Rats in the minocycline group were given 40 mg/kg·d minocycline by gavage;rats in the low-,medium,and high-dose groups were given 4,8,and 16 g/kg·d Shujin Jiannao Prescription granules by gavage,respectively;and rats in the normal group and control model group were given an equal dose of normal saline by gavage.Medication in each group was given once a day for 1 week.The rats in each group were evaluated behaviorally using suspension test,abnormal involuntary movement score,and Bederson score.The pathological changes of the cerebral cortex were observed by hematoxylin-eosin staining.The levels of tumor necrosis factor α,interleukin 1β,and interleukin 10 in the cerebral cortex were determined using ELISA.The positive expressions of Janus kinase 2(JAK2),phosphorylated Janus kinase 2(p-JAK2),phosphorylated signal transducer and activator of transcription 3(p-STAT3)in the cerebral cortex were detected using immunohistochemistry.The protein expression levels of JAK2,p-JAK2,and p-STAT3 were detected using western blot. RESULTS AND CONCLUSION:Compared with the normal group,the suspension test score and involuntary movement score were decreased in the control model group(P＜0.01 or P＜0.05).The pathological results showed structural disruption of nerve cells,formation of large numbers of vacuoles,cell swelling,and increased intercellular space in the control model group.In addition,the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were significantly increased(P＜0.01),the expression of interleukin 10 was decreased(P＜0.05),and the protein expressions of JAK2,p-JAK2,and p-STAT3 in the cerebral cortex were significantly increased(P＜0.01)in the control model group compared with the normal group.Compared with the model group,minocycline and Shujin Jiannao Prescription at each dose could improve the behavioral indexes of rats(P＜0.01 or P＜0.05)and ischemic-hypoxic pathological changes were attenuated,with only a small amount of necrotic nerve cells and a few vacuoles,and reduced intercellular space.Moreover,the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were decreased in each drug group compared with the control model group(P＜0.05),while the protein expressions of JAK2,p-JAK2,and p-STAT3 in the cerebral cortex were significantly decreased(P＜0.01).The most obvious improvement was observed in the high-dose Shujin Jiannao Prescription group.To conclude,Shujin Jiannao Prescription can inhibit inflammation in the cerebral cortex of rats with hypoxic-ischemic brain injury.The mechanism may be related to the regulation of the JAK2/STAT3 signaling pathway.
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BACKGROUND:Perinatal hypoxic-ischemic brain injury is one of the most common causes of cerebral palsy.Shujin Jiannao Prescription is an experienced formula for treating cerebral palsy and improving blood supply to the brain developed by the Dongzhimen Hospital,Beijing University of Chinese Medicine. OBJECTIVE:To explore the possible mechanism of Shujin Jiannao Prescription in treating hypoxic-ischemic cerebral palsy. METHODS:Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into six groups.There were 12 rats in each of the control and model groups as well as 10 animals in each of the minocycline group,and the low-,medium-,and high-dose groups of Shujin Jiannao Prescription.The neonatal rat ischemic-hypoxic cerebral palsy model was established in all groups except for the control group.After successful modeling,rats in each drug group were respectively gavaged with minocycline and Shujin Jiannao Prescription at a dose of 4,8,and 16 g/kg per day for 1 week.Body mass of rats was measured and behavioral changes were detected before and after drug administration.Hematoxylin-eosin staining was used to observe the histomorphology of hippocampal CA1 region of rat brain tissue,and immunohistochemistry and western blot were used to detect the expression levels of Bcl-2,Bax,and Caspase-3 in the brain tissue of rats. RESULTS AND CONCLUSION:Compared with the model group,medium-and high-dose Shujin Jiannao Prescription significantly increased the body mass of rats(P<0.05).Compared with the model group,minocycline effectively prolonged the suspension time of ischemic-hypoxic cerebral palsy rats(P<0.05),while medium-and high-dose Shujin Jiannao Prescription significantly prolonged the suspension time,shortened the inclined plane test time,and increased the Longa score of rats(P<0.05).The pathological results showed that after drug intervention,only a small number of neuronal cells in the brain tissue of rats were necrotic,the cells were more neatly arranged,the cell structure was more complete,and only part of the cell nuclei became smaller.Compared with the model group,minocycline and medium-and high-dose Shujin Jiannao Prescription reduced the expression of Bax Caspase-3(P<0.05),medium-and high-dose Shujin Jiannao Prescription increased the expression of Bcl-2(P<0.05),and Bcl-2/Bax protein expression was increased in minocycline and three Shujin Jiannao Prescription groups(P<0.05).In addition,the protein expression was increased in a dose-dependent manner after intervention with Shujin Jiannao Prescription,and there was no significant difference between the minocycline and three Shujin Jiannao Prescription groups(P>0.05).To conclude,the mechanism by which Shujin Jiannao Prescription treats ischemic-hypoxic cerebral palsy in rats may be to enhance the expression of anti-apoptotic protein Bcl-2,inhibit the expression of pro-apoptotic protein Bax,and reduce the expression of Caspase-3,ultimately inhibiting the apoptosis of hippocampal neuronal cells in rats with cerebral palsy.Within a certain range,the higher dose of Shujin Jiannao Prescription indicates the better therapeutic effect,and the high-dose Shujin Jiannao Prescription is as effective as minocycline.
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ObjectiveTo investigate the impact of icariin （ICA） on autophagy in glucocorticoid-induced bone microvascular endothelial cells （BMECs） mediated by the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway. MethodBMECs were isolated and cultured from femoral heads obtained during total hip arthroplasty and identified using immunofluorescence staining. The experimental cells were divided into four groups： A control group， a glucocorticoid group （100 mg·L-1 hydrocortisone）， an ICA group （100 mg·L-1 hydrocortisone+6.7×10-3 mg·L-1 ICA）， and a Rapamycin group （100 mg·L-1 hydrocortisone+6.7×10-3 mg·L-1 ICA+1 mg·L-1 rapamycin）. Autophagy in BMECs was induced using 100 mg·L-1 hydrocortisone. LC3 fluorescence staining was used to observe the peak of autophagy at different time points. Western blot analysis was employed to analyze the expression of autophagy-related proteins and PI3K/Akt/mTOR pathway proteins in each group. Electron microscopy was used to observe autophagosomes and autolysosomes in the cells. ResultHydrocortisone at 100 mg·L-1 induced autophagy in BMECs， reaching a peak at around 5 hours， which then declined with further intervention. Compared to the control group， the glucocorticoid group showed cell membrane damage， disordered organelle arrangement， and a large number of autophagosomes and autolysosomes. Compared to the glucocorticoid group， the ICA group had more intact cell membranes， sparser organelle arrangement， and fewer autophagosomes and autolysosomes. Compared to the ICA group， the Rapamycin group showed cell membrane damage， disordered organelle arrangement， and more autophagosomes and autolysosomes. Compared to the control group， the glucocorticoid group had significantly increased expression of light chain 3B （LC3B）， Atg4B， and p62 （P<0.01）. Compared to the glucocorticoid group， the ICA group showed significantly decreased expression of LC3B， Atg4B， p62， and Beclin-1 （P<0.01）. Compared to the ICA group， the Rapamycin group had significantly increased expression of Atg4B and p62 （P<0.01）. Compared to the control group， the glucocorticoid group had significantly decreased expression of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR （P<0.01）. Compared to the glucocorticoid group， the ICA group showed significantly increased expression of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR （P<0.01）. Compared to the ICA group， the Rapamycin group had significantly decreased expression of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR （P<0.01）. Ubiquitination levels were significantly decreased in the glucocorticoid group compared to the control group （P<0.01）. Compared to the glucocorticoid group， ubiquitination levels were significantly increased in the ICA group （P<0.01）， and significantly decreased in the Rapamycin group compared to the ICA group （P<0.01）. ConclusionThe glucocorticoid-induced autophagy in BMECs is time-dependent. ICA inhibits glucocorticoid-induced autophagy in BMECs， and this effect may be related to the regulation of the PI3K/Akt/mTOR pathway.
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Diabetic osteoporosis （DOP） is a kind of bone complication caused by diabetes， which is characterized by the decrease of bone mineral density， the change of bone microstructure and the increase of bone fragility. The process of DOP is closely related to high glucose， insulin resistance， oxidative stress and other mechanisms. The Wnt/β-catenin signaling pathway plays an important role in mediating insulin resistance and bone metabolic balance in diabetes. Regulation of Wnt signal transduction promotes the expression of glycogen synthase kinase-3β（GSK-3β）phosphorylation and improves glucose and lipid metabolism. The Wnt/β-catenin signaling pathway is also an important way regulating osteocyte-driven bone remodeling， which not only plays an important regulatory role in the balance between osteoblasts and osteoclasts and improve bone metabolic homeostasis， but also promotes the expression of osteopontin， osteocalcin and type Ⅰ collagen， and improves bone proliferation and osteogenic differentiation by regulating the Wnt pathway. In recent years， the research of traditional Chinese medicine （TCM） in the prevention and treatment of DOP has gradually increased， and the exploration of TCM to interfere with the Wnt pathway to improve DOP has made some progress. This paper collects and summarizes the studies on the Wnt signaling pathway in glucose metabolism， bone metabolism and DOP worldwide in the past decade， as well as the related literature on the intervention of DOP by TCM compounds （classical and other compounds）， single Chinese medicine and TCM monomers based on the Wnt pathway， in order to provide a reference and direction for the development of new drugs for clinical prevention and treatment of DOP.
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ObjectiveThis study aims to investigate the therapeutic effect of Tangbikang granules（TBK） on type 2 diabetes mellitus （T2DM） complicated with non-alcoholic fatty liver disease （NAFLD） and to elucidate the underlying mechanism. MethodT2DM and NAFLD were induced in ZDF rats， which were then respectively treated （ig） with low-dose （0.625 g·kg-1）， medium-dose （1.25 g·kg-1）， and high-dose （2.5 g·kg-1） TBK for 12 weeks. Fasting blood glucose （FBG） and body mass were recorded every 4 weeks during the treatment. One week before sampling， the feed intake of rats was detected， and after 12 h night fasting， oral glucose tolerance test （OGTT） was performed. The area under the curve （AUC） was used to evaluate glucose tolerance， and the homeostatic model assessment for insulin resistance （HOMA-IR） was calculated. Blood in abdominal aorta and liver were collected for determination of blood glucose and lipid metabolism indexes： Fasting serum insulin （FINS）， serum total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， high density lipoprotein cholesterol （HDL-C）， and nonesterified fatty acids （NEFA）. The liver was weighed to calculate the liver index， and the liver tissue morphology was observed and analyzed based on hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. The protein levels of insulin receptor substrate （IRS）， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt） and phosphorylated IRS and Akt were detected by Western blotting. All data were analyzed by SPSS 20.0. ResultThe feed intake of the model group was higher than that in the normal group （P<0.01）， and the feed intake the administration groups was lower than that in the model group （P<0.05， P<0.01）. At the 8th and 12th week， the body mass in the model group was lower than that in the normal group （P<0.01）. Compared with the model group， TBK reduced FBG in a concentration-dependent manner. The blood glucose level in OGTT and AUC in the model group were higher/larger than those in the normal group （P<0.01）. The blood glucose value in OGTT was decreased in TBK groups and the metformin group compared with that in the model group， and AUC in the administration groups was significantly different from that in the model group （P<0.01）. The serum level of FINS and HOMA-IR in the model group were higher than those in the normal group （P<0.01）， and they were lower in the TBK groups than in the model group （P<0.01）. Serum levels of TG， TC， HDL-C， NEFA （P<0.05， P<0.01）， and LDL-C were higher in the model group than in the normal group. Serum levels of TG， TC， LDL-C， and NEFA in the TBK groups were lower than those in the model group， and the levels of TG， LDL-C， and NEFA in TBK groups were concentration-dependent （lowest levels in high-dose TBK group）. Compared with the model group， high-dose TBK significantly increased the level of HDL-C （P<0.05）. Liver index of the model group was higher than that in the normal group （P<0.01）. The liver index of the administration groups showed a decreasing trend with no significant difference from that in the model group. As for the HE staining result of liver， the model group had unclear structure of liver lobule， enlarged cells of different sizes， and obvious steatosis of hepatocytes. TBK of all doses alleviated liver injury， particularly the high dose. For the PAS staining， compared with the normal group， the model group demonstrated significant fat vacuoles and significant reduction in purplish red glycogen granules in the cytoplasm. The staining results of high- and medium-dose groups of TBK were more similar to the normal group. Western blot was used to detect the protein expression of liver tissue. The expression of PI3K protein， p-IRS1/IRS1， and p-Akt/Akt in the model group were lower than those in the normal group （P<0.01）， and they were higher in the high-dose TBK group than in the model group （P<0.01）. ConclusionTBK exerts therapeutic effect on T2DM combined with NAFLD in ZDF rats by activating the typical PI3K signaling pathway.
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ObjectiveTo explore the mechanism of Tangbikang granules （TBK） against diabetic peripheral neuropathy （DPN） based on network pharmacology and in-vivo experiment. MethodThe active components in medicinals of TBK and their target genes were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. The active components of the medicinals which are not included in TCMSP were searched from previous research. After the analysis of drug-likeness by SwissADME， the target genes of them were predicted with SwissTargetPrediction. DPN-related target genes were retrieved from GeneCards. The common targets of the disease and the prescription were the hub genes of TBK against DPN， which were uploaded to Metascape for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. High-sugar and high-fat diet and low-dose streptozotocin （STZ， ip） were employed to induce diabetes in rats， and then the model rats were respectively treated with low-dose （0.625 g·kg-1）， medium-dose （1.25 g·kg-1）， and high-dose （2.5 g·kg-1） TBK for 12 weeks. Sensory nerve conduction velocity （SNCV） was evaluated. After hematoxylin and eosin （HE） staining， the sciatic nerve was observed under light microscope to examine the nerve damage. Real-time PCR was performed to detect the gene expression of adenosine monophosphate-activated protein kinase （AMPK） pathway-related targets in rat sciatic nerve， and Western blot to measure the protein expression of AMPK and phosphorylated （p）-AMPK in rat sciatic nerve. ResultThe main active components of TBK， such as quercetin， kaempferol， β-sitosterol， leech pteridine A， stigmasterol， and baicalein were screened out， mainly acting on interleukin-6 （IL-6）， tumor necrosis factor （TNF）， protein kinase B （Akt）， JUN， and HSP90AA1 and signaling pathways such as AMPK， nuclear factor-κB （NF-κB）， and Janus kinase/signal transducer and activator of transcription （JAK/STAT）. Molecular docking results showed that β-sitosterol and stigmasterol had high binding affinity with IL-6， TNF， JUN， and HSP90AA1. As for the animal experiment， compared with the normal group， model group had low SNCV of sciatic nerve （P<0.01）， disordered and loose myelinated nerve fibers with axonotmesis and demyelinization， low mRNA expression of AMPKα， AMPKβ， peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）， Sirtuin 3 （SirT3）， mitochondrial transcription factor A （TFAM）， and low p-AMPK/AMPK ratio in sciatic nerve （P<0.05， P<0.01）. Compared with the model group， TBK of the three doses raised the SNCV （P<0.01）， restored nerve morphology and nerve compactness， and increased the mRNA expression of AMPKα， AMPKβ， PGC-1α， SirT3， and TFAM （P<0.05， P<0.01）. The ratio of p-AMPK/AMPK in the high-dose and medium-dose TBK groups was higher than that in the model group （P<0.01）， while the protein expression in the low-dose TBK group was insignificantly different from that in the model group. ConclusionTBK exerts therapeutic effect on DPN through multiple pathways and targets. The mechanism is that it activates and regulates AMPK/PGC-1α/SirT3 signaling， which lays a basis for further study of TBK in the treatment of DPN.
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ObjectiveTo explore the effect of Tangbikang granules （TBK） on sciatic nerve inflammation in diabetic rats through modulation of adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor （NF）-κB pathway. MethodSD rats were fed with high-fat and high-sugar diet for 8 weeks and then treated with streptozotocin （STZ， ip） at 35 mg·kg-1 for modeling. Then the rats were randomized into diabetes group， low-dose （0.625 g·kg-1）， medium-dose （1.25 g·kg-1）， and high-dose （2.5 g·kg-1） TBK groups， and lipoic acid group （0.026 8 g·kg-1） according to body weight and blood glucose level， and a normal group was designed. After modeling， administration began and lasted 12 weeks. The body mass， blood glucose level， and thermal withdrawal latency （TWL） of the rats were detected before treatment and at the 4th， 8th， and 12th week of administration. At the 12th week， the sciatic nerve was collected for hematoxylin-eosin （HE） and Luxol fast blue （LFB） staining， and the structural changes of sciatic nerve were observed under scanning electron microscope. The levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in sciatic nerve were measured by enzyme-linked immunosorbent assay （ELISA）， and the levels of AMPK， phosphorylated （p）-AMPK， and NF-κB proteins in the sciatic nerve were measured by Western blot. ResultThe blood glucose concentration and TWL in the model group were higher than those in the normal group at each time point （P<0.01）. The levels of IL-1β， TNF-α， and NF-κB protein in sciatic nerve in the model group were higher than those in the normal group （P<0.01）， and the p-AMPK/AMPK ratio was smaller than that in the normal group （P<0.01）. Compared with the model group， TBK of the three doses lowered the TWL （P<0.05， P<0.01） and the levels of IL-1β， TNF-α， and NF-κB protein in sciatic nerve of rats （P<0.05， P<0.01）， and high-dose and medium-dose TBK raised p-AMPK/AMPK （P<0.05， P<0.01）. The sciatic nerve fibers were orderly and compact with alleviation of demyelination in rats treated with TBK compared with those in the model group. ConclusionTBK improves the function of sciatic nerve and alleviates neuroinflammation in diabetic rats. The mechanism is the likelihood that it up-regulates the expression of AMPK in the AMPK/NF-κB pathway and inhibits the expression of downstream NF-κB， thereby alleviating the neuroinflammation caused by high levels of inflammatory factors such as IL-1β and TNF-α due to NF-κB activation.
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Diabetic peripheral neuropathy （DPN） is a symptom and/or sign of peripheral nerve dysfunction that occurs in patients with diabetes mellitus when other causes are excluded. DPN， one of the most common complications of diabetes mellitus， can lead to disability， foot ulcers， and amputation at a later stage. Its pathogenesis is closely related to high glucose-induced inflammatory damage， oxidative stress， mitochondrial disorders， and apoptosis in neural tissues. The p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway is a key mechanism mediating the expression of inflammatory factors， oxidative factors， and apoptotic factors of neural tissues in DPN. The inflammatory response， oxidative stress damage， and apoptosis， induced by the activation of p38 MAPK phosphorylation by factors such as high glucose， can cause cell lipid peroxidation， protein modification， and nucleic acid damage， which results in axonal degeneration and demyelination changes. The current treatment of DPN with western medicine has obvious shortcomings such as adverse effects and addictive tendencies. In recent years， the research on traditional Chinese medicine （TCM） in the prevention and treatment of DPN has gradually increased， and the exploration of Chinese medicine intervention in the p38 MAPK pathway transduction to improve DPN has advanced. The present study reviewed the relations of the p38 MAPK pathway with insulin resistance and peripheral neuropathy and summarized the molecular biological mechanisms involved in the pathological process of DPN， such as inflammation regulation， oxidative stress， polyol pathway regulation， and Schwann cell apoptosis in the past 10 years. In addition， the literature on Chinese medicine monomers， Chinese patent medicines， and Chinese medicine compounds in inhibiting inflammatory reactions， oxidative injury， and apoptosis of DPN peripheral nerves based on the p38 MAPK pathway， resisting axonal degeneration and demyelination changes， improving sensory and motor abnormalities， relieving peripheral pain sensitization， and facilitating nerve conduction mechanism to provide references for the development of new drugs for clinical prevention and treatment of DPN.
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Objective:The effect of serum thyrotropin receptor antibody (TRAb) on permanent hypothyroidism (HT) after 131I treatment in Graves disease patients and its predictive value Methods:479 Graves' disease patients who underwent 131I treatment at the Nuclear Medicine Department of North China University of Technology Affiliated Hospital from October 2013 to October 2021 were selected. Among them, 350 cases (permanent HT group) had permanent HT during follow-up, while 129 cases (non permanent HT group) did not. Collect general clinical data such as gender, age, degree of thyroid enlargement, as well as indicators such as iodine intake rate, thyroid function, and treatment dose 24 hours before treatment, from two groups of patients. Compare the general clinical data and pre treatment levels of various detection indicators between two groups of patients, analyze the risk factors for permanent HT in Graves disease patients after 131I treatment, and evaluate the predictive value of pre treatment serum TRAb levels, and evaluate the consistency between the predicted results and clinical diagnosis. The econometric data with a normal distribution is represented by xˉ± s, and two independent sample t-tests are used for comparison between the two groups; The econometric data that do not conform to the normal distribution are represented by M（ Q1， Q3）, and the Wilcoxon rank sum test is used for comparison between the two groups; The counting data is represented as an example (%), and the comparison between the two groups is conducted using the four grid χ 2 test, while the comparison of grade data is conducted using the Willcoxon rank sum test; The logistic regression model was used for multivariate analysis. Draw a subject work characteristic curve to evaluate the predictive efficacy of TRAb, and screen the predictive threshold based on the Chayoden index; Calculate sensitivity and specificity, and evaluate the consistency between the predicted results and clinical diagnosis by calculating Kappa values. Results:There were no statistically significant differences in gender, age, degree of thyroid enlargement, 24-hour iodine uptake rate, serum thyroid stimulating hormone, free triiodothyronine, free thyroxine levels, and 131I treatment dose between the permanent HT group and the non permanent HT group (all P>0.05); The pre treatment TRAb levels in the permanent HT group were higher than those in the non permanent HT group [14.51(4.95,33.58) U/L vs 3.40(1.67,16.5) U/L], with a statistically significant difference ( Z=5.87, P<0.001). The results of multivariate logistic regression analysis showed that pre treatment TRAb levels were a risk factor for permanent HT in Graves' disease patients after 131I treatment (odds ratio=1.042,95% confidence interval: 1.025-1.059, P<0.001). The area under the working characteristic curve for predicting permanent HT in Graves' disease patients after 131I treatment with pre-treatment TRAb levels is 0.674 (95% confidence interval: 0.616~0.732), and the optimal critical value is 7.025 U/L. Using TRAb>7.025 U/L before treatment as the standard for predicting postoperative permanent HT in patients, the sensitivity and specificity were 73.7% and 75.2%, respectively. The predicted results showed moderate consistency with clinical diagnosis ( Kappa=0.426). Conclusions:The pre treatment TRAb level is a risk factor for permanent HT in Graves disease patients after 131I treatment ( P<0.001), and the diagnostic efficacy of permanent HT is best when TRAb>7.025 U/L.
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Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores. In this study, we demonstrate that the upregulated intestinal transporter (PCFT), which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats, mediates the uptake of the folic acid-grafted nanoparticles (FNP). Specifically, the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway, Golgi-targeting pathway and basolateral exocytosis, featuring a high oral insulin bioavailability of 14.4% in the diabetic rats. Conversely, in cells with relatively low PCFT expression, the positive surface charge contributes to the cellular uptake of FNP, and FNP are mainly degraded in the lysosomes. Overall, we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway. This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.
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The majority patients of differentiated thyroid carcinoma (DTC) with indolent progression have general good prognosis after standard primary treatments including surgery, thyroid stimulating hormone (TSH) suppression and radioactive iodine (RAI) therapy. However, there are still some patients suffered from recurrence or distant metastasis after initial treatment. They may lose the ability of uptaking iodine during their natural course of disease or treatment and could not benefit from subsequent RAI treatment, which will result in radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). Options are very limited for RAIR-DTC patients, which is associated with a poor prognosis. Recently, with the research advances on the molecular mechanism of RAIR-DTC, redifferentiation combined with RAI therapy have been increasingly used to treat RAIR-DTC, and some outcomes are quite encouraging. This paper reviews the progress of signaling pathway inhibitors, histone deacetylase inhibitors, DNA methyltransferase inhibitors, retinoids and peroxisome proliferator-activated receptor agonists in redifferentiating therapy of RAIR-DTC.
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@#The genome, replication mode and nosogenesis of duck hepatitis B virus are similar to those of human hepatitis B virus. In addition, the natural host of duck hepatitis B virus is readily available, cheap and has a high success rate of infection. Therefore, duck hepatitis B virus-infected models have been widely used for drug screening, pharmacological and pathological studies. For drug screening, the model is easy to obtain with high infection success rate and good stability. In the pharmacological research, the model can maintain high levels of viral DNA replication in the hepatocytes and exhibit significant damaged liver phenotypes which can reflect the pharmacological effects of drugs with different mechanisms. Also in the pathologic mechanisms research, the model has entire virus life cycle and maintains a pool of covalent closed-loop DNA in the hepatocytes, which can help scientific researchers better understand human hepatitis B virus. This article reviews the applications of duck hepatitis B animal model in drug screening, pharmacological and pathological studies, also outlooks the application prospect of this model.
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Objective To construct a grading nursing care system at public hospitals based on the severity of illness and activities of daily living ( ADL). Methods Multi-center stratified random sampling was used to investigate the general adult patients hospitalized in 12 wards of six tertiary-level hospitals in the eastern, central and western parts of China from January to December of 2016. The Barthel index and simple clinical score ( SCS) were used to evaluate their ADL and severity of illness, while a customized direct nursing hour scale was applied to record the direct nursing time needed by patients in 24 hours. Nursing grades were defined according to different conditions and ADL and to the difference of patient needs of 24 h direct nursing hours. Results 7 200 patients were investigated in total, and 7 073 effective questionnaires were collected (98. 24% ). Seven new grades of nursing care were defined based on patients′ severity of illness, ADL and different 24 h direct nursing time. These grades match the existing four grading nursing care levels to become refined sub-levels. Conclusions Patients can be graded according to their conditions, ADL and the 24 h direct nursing time needed. Such a new method is more objective, specific and quantitative than before, conducive to upgrading fine management level of nursing.
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Traditional Chinese medicine shows good hypoglycemic effect with mild efficacy, long duration and few adverse reac-tions. In recent years, the researches on the hypoglycemic effect of Ruikang Hospital Affilliated to traditional Chinese medicine mainly started from the mechanism of new target protein and pathway, for example, Chinese medicine monomers or compounds including as-tragalus polysaccharide, curcumin, berberine, emodin, total saponins of momordicacharantia, total saponins of momordicacharantia, Yitangkang, Jiangtang Sanhuang tablets, Jianpixiaokefang and Tangnaikang granule can activate Adenosine monophosphate ( AMP)-activated protein kinase ( AMPK) to play hypoglycemic effect.
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DNA typing of biological samples is an important step in performing individual identification and paternity testing in forensic applications. In practice, the detection of complex biological samples and the identification of complex kinships are challenging current biological technologies. Novel DNA technologies are also introduced into forensic genetics to improve the power of analysis. Next-generation sequencing (NGS) has several advantages, such as high-throughput and low cost, and can obtain detailed DNA sequences and relative contents of targeted regions, which will improve the detection of biological samples to help the analysis of forensic cases. The application of NGS in forensic genetics has received extensive attention and reports on the application of NGS in forensic genetics are increasing. In this study, we summarized the progress in the application research of NGS in the forensic genetics including the detection of genetic markers and their analytical methods. This will provide guides for related studies and forensic applications.
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RNA has received m ore attention in the field of forensic m edicine and the developm ent of the new biological m arkers based on RNA show s great significance in the analysis of com plex cases. circular RNA (circRNA ) is a kind of non-coding RNA w hich is w idely reported recently. A lthough the regulatory m echanism s of generation and expression are not fully clear, the existing research indicates that circRNA has im portant biological functions. C ircRNA has a cell-type-specific expression w ith great stability and a high expression level, w hich m akes it m eaningful in forensic applications potentially. In this paper, the research progress, the generation and regulation of circRNA as w ell as its biological characteristics and functions are sum m arized, w hich w ill provide references for related studies and foren-sic applications.
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Objective To conduct a single-center retrospective analysis on the distribution characteristics and prevalence of idiopathic membranous nephropathy (IMN) patients diagnosed with pathology for the past 16 years,to investigate diagnostic and differential diagnostic value of serum antiphospholipase A2 receptor antibodies (PLA2R-Ab),and to evaluate the correlation between PLA2R-Ab and clinical disease activity.Methods (1) 6996 biopsy-proven primary glomerular nephropathy (PGN) patients,including 1567 IMN cases,admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2000 to December 2015 were involved.Demographics and pathological type were gathered from all patients.(2) 433 cases receiving renal biopsy and testing PLA2R-Ab from June 2015 to December 2015 were involved,with their clinical and laboratorial data being collected.During the period patients' follow-up time,therapeutic schedule and laboratory results were recorded.Results (1) IMN accounted for 22.4％ of primary glomerular disease,and patients above 40 years old accounted for more than 60％ of the IMN.(2) The sensitivity and specificity of serological PLA2R-Ab were 58.1％(95％CI 47.0％-68.5％) and 98.6％(95％CI 95.6％-99.6％) respectively.PLA2R-Ab positive rate was affected by immunosuppression therapy.(3) The PLA2R-Ab titers wasn't correlated with 24-hour urinary protein (r=-0.017,P=0.887),serum albumin (r=-0.072,P=0.549) and urinary red blood cell count (r=-0.030,P=0.802).There was no difference between PLA2R-Ab positive positive and PLA2R-Ab negative on proportion of IMN pathological stage Ⅰ-Ⅱ (P ＞ 0.05).Thirteen cases of patients with PLA2R-Ab positive were all prescribed glucocorticoid combined with immunosuppressant.After (2.21± 1.09) months,the decrease of PLA2R-Ab titers was in accordance with 24-hour urinary protein quantity descending and serum albumin ascending (P ＜ 0.05).Condusions The incidence of IMN increase year by year,especially in the mid-aged and the elderly.Serum PLA2R-Ab correlates not with IMN pathological stage,but with the development of IMN.Monitoring PLA2R-Ab titers individually may access the efficiency of treatment.
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@#The purpose of this study was to investigate the formation thermodynamics of baicalein(BE)-nicotinamide(NCT)cocrystals in three solvents including ethyl acetate, acetone and trichloromethane. The solubilities of BE, NCT and BE-NCT in the above solvents at 25 °C were measured. Ternary phase diagrams(TPDs)of the BE-NCT-solvent systems were established. The non-linear fitting equation according to 1 ∶1 complexation mechanism of BE-NCT cocrystals demonstrated a good correlation between calculated and experiment data. ΔG0< 0 suggested that BE-NCT cocrystal formation was a spontaneous process. Among the organic solvents studied, the absolute value of ΔG0 in trichloromethane was significantly lower than that in the other two solvents. In addition, the cocrystallization zone in trichloromethane was far away from stoichiometric line. This study provides a theoretical foundation for solvent selection and preparation-condition optimization of BE-NCT cocrystals.